22 Physiology of the Kidney 



be handled by the tubule cells per unit time. The net conse- 

 quence of this circumstance is that at high plasma levels of 

 creatinine the total creatinine clearance is depressed towards 

 the level of the inulin clearance (see 40). The same may be 

 said of the excretion of phenol red''^ and diodrast, hippuran 

 and iopax, which have been examined by other investiga- 

 tors.^''^^ In every instance where an adequate examination 

 has been possible, it has been shown that, just as in the 

 case of tubular reabsorption, so in tubular excretion there 

 exists a limitation in tubular activity, which takes the form 

 of a maximal rate of excretion."' When the plasma con- 

 centration of any of these substances is raised above a criti- 

 cal level the tubular mechanism becomes saturated, so to 

 speak, and excretes the substance at a maximal rate. This 

 maximal rate has, of course, a different value for each sub- 

 stance. Again we may designate the maximal rate by Tm, 

 and speak of the creatinine Tm and phenol red Tm, dio- 

 drast Tm, etc., and these values will of course differ in dif- 

 ferent individuals, depending upon the size of the kidneys 

 or the number of normal nephrons. The maximal rate of 

 tubular excretion may be determined by deducting the quan- 

 tity filtered through the glomeruli from the total quantity 

 excreted per minute, when the plasma level has been raised 

 to such a level as to load the tubule cells to full capacity. The 

 curves shown in Figure 3 relating the creatinine, phenol red 

 and diodrast clearances to plasma concentration, are calcu- 

 lated on the basis of average observed Tm values in normal 

 man. 



This diagram serves not only to illustrate certain prin- 



'■•"The glomerular excretion of all these substances, with the exception of creatinine, 

 is complicated by the circumstance that they are in part bound to plasma proteins in ap- 

 parently all species and are not completely filterable. Data are available for correcting 

 for this protein binding, although we need not detail these corrections here (45,49). 



